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Optogenetic research on molecular switches for nerve cells

Publication by researchers at Bielefeld University in a young field of research into light-controlled cells

Optogenetics uses light to control neurons and other electrically excitable cells. These cells are genetically modified so that they can be targeted specifically by light of a certain wavelength. In the specialist journal Trends in Biochemical Sciences, two scientists at Bielefeld, Dr. Arash Kianianmomeni and Professor Dr. Armin Hallmann, report on new optogenetic tools that can be used not only to switch on neurons quickly but also to switch them off again quickly without disturbing the natural processes in the cell. These molecular light sensors open up new possibilities – not only for basic research in neurobiology and cell biology but also for biomedical applications.

The new research field of optogenetics emerged in 2002 with the discovery of a light-activated protein in green algae known as channelrhodopsin. This protein is located in the outer membrane of the alga cell. When stimulated by light of a certain wavelength, it opens a channel to allow charged particles (ions) to pass through the membrane. In flagellate green algae, these light-sensitive proteins serve the function of light perception, enabling them, for example, to swim directly towards the light. The path from light-sensitive proteins found in green algae to molecular tools in brain research can sometimes be very short: in a nerve cell that can be excited electrically (a neuron), letting charged particles pass through the cell membrane triggers a nerve impulse. If these light-sensitive algae proteins can be introduced into the nerve cells by genetic engineering, these cells can then be activated non-invasively with light. As soon as optogenetic researchers succeed in finding out more about how to control nerve cells through light, it will become possible to influence even brain functions. ‘Nonetheless, a molecular switch needs to be able to switch off just as quickly as it is switched on,’ explains Dr. Arash Kianianmomeni. However, up to now, the latter has not been possible.

The first effective molecular off-switch was identified yet again in algae (cryptophyta). ‘Through targeted genetic engineering based on the 3D structure of the proteins we can now even turn on-switches into off-switches. This makes it possible to quickly switch on nerve cells modified through genetic engineering with light of a certain wavelength and to switch them off again quickly with light of a different wavelength,’ says Professor Dr. Armin Hallmann. Optogenetics also makes it possible to equip only certain types of cells within a tissue with such a ‘light switch’.

Approximately 1,500 laboratories throughout the world are currently working on diverse aspects of light-activated on- and off-switches. Most of this work is basic research. With the help of molecular switches, it is now possible to study the networks of nerve cells in living animals. Of particular interest here are animals that develop symptoms similar to serious human diseases. Optogenetics already plays an important role in clarifying brain functions and in carrying out research on neurological disorders such as Parkinson’s, Alzheimer’s, attention deficit hyperactivity disorder (ADHD), pain disorders, addictions, Tourette’s syndrome, and epilepsy. ‘In the long term, we can hope to develop optogenetically based treatment options for these neurological disorders,’ says Arash Kianianmomeni. ‘The light-dependent off-switch mentioned above could also be particularly relevant for disorders such as epilepsy or Tourette’s syndrome, because these are caused by overstimulation in certain areas of the brain.’